Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

These results suggest that activation of phospholipase A2 after antigen exposure triggers an increase in leukotriene synthesis resulting in inflammatory cell influx into the airway and contraction of bronchial smooth muscle. That is, it was demonstrated that inhaled antigen concerns with IgE-mast cell system, but, on the other hand it might act as non specific stimuli.
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PMID:Biochemical changes in airways after antigen inhalation. 255 40

Five structurally related heptadecapeptides rich in hydrophobic amino acids have been discovered in the venom of the bumblebee Megabombus pennsylvanicus. We have named them bombolitin I (Ile-Lys-Ile-Thr-Thr-Met-Leu-Ala-Lys-Leu-Gly-Lys-Val-Leu-Ala-His-Val-NH2 ), bombolitin II (Ser-Lys-Ile-Thr-Asp-Ile-Leu-Ala-Lys-Leu-Gly-Lys-Val-Leu-Ala-His-Val-NH2 ), bombolitin III (Ile-Lys-Ile-Met-Asp-Ile-Leu-Ala-Lys-Leu-Gly-Lys-Val-Leu-Ala-His-Val-NH2 ), bombolitin IV (Ile-Asn-Ile-Lys-Asp-Ile-Leu-Ala-Lys-Leu-Val-Lys-Val-Leu-Gly-His-Val-NH2 ), and bombolitin V (Ile-Asn-Val-Leu-Gly-Ile-Leu-Gly-Leu-Leu-Gly-Lys-Ala-Leu-Ser-His-Leu-NH2 ). Bombolitins are structurally and functionally very similar. They lyse erythrocytes and liposomes, release histamine from rat peritoneal mast cells, and stimulate phospholipase A2 from different sources. The threshold dose is 0.5-2.5 micrograms/ml depending on the peptide and the bioassay. Bombolitin V is as potent as the well-known melittin in lysing guinea pig erythrocytes (ED50 = 0.7 microgram/ml = 4 X 10(-7) M) and is 5 times more potent than mastoparan in causing mast cell degranulation, making it one of the most potent degranulating peptides discovered so far (ED50 = 2 micrograms/ml = 1.2 X 10(-6) M). The bombolitins represent a unique structural class of peptides but they have the same biological properties as melittin (from honeybees), mastoparan (wasps, hornets, and yellow jackets), and crabrolin (European hornets). This unusual circumstance (peptides with different amino acid sequences having the same biological properties) may be a manifestion of their amphiphilic nature, a property these peptides have in common.
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PMID:Bombolitins, a new class of mast cell degranulating peptides from the venom of the bumblebee Megabombus pennsylvanicus. 257 59

Intraalveolar leukocytosis is integral in initiating and perpetuating airspace inflammatory reactions. We used intratracheal instillation of silica suspensions in adult male rats to cause neutrophil flux (32% increase over saline controls) without creating a protein leak, so simulating an early inflammatory response. We examined the in vivo effects of a known phospholipase A2 inhibitor (mepacrine) and the two mast cell active agents (cyproheptadine and reserpine) on lung lavage fluid chemotactic capability, alveolar macrophage (AM) production of chemotactic factor(s), and neutrophil diapedesis. Only mepacrine significantly depressed the leukocytosis (from 32% to 8% of total cells), with a similar diminution in AM chemotaxin production. Separate in vitro experiments using mepacrine-pretreated neutrophils and macrophages gave evidence that mepacrine: (1) diminishes neutrophil response to chemotaxin(s), (2) inhibits spontaneous, random neutrophil movement, and (3) diminishes macrophage-derived chemotactic factor production. These observations suggest that the earliest events in alveolar inflammatory reactions probably involve local production of chemotactic factors by AM, and that mepacrine's anti-inflammatory action results from inhibitory influences on both macrophage and neutrophil populations.
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PMID:Mepacrine impairs neutrophil response after acute lung injury in rats. Effects on neutrophil migration. 284 50

The protective effects on mast cell activation were compared between a new antiallergic agent, KP-136 and disodium cromoglycate (DSCG), both of which inhibited the immunological degranulation of rat peritoneal mast cells. The IC50 was 0.03 micrograms/ml for KP-136 and 4.7 micrograms/ml for DSCG. KP-136 predominantly acted on the early stage of mast cell activation processes and inhibited the immunological increase in 45Ca uptake. KP-136 also inhibited A23187- and heat-induced degranulation and heat-induced hemolysis. In addition, KP-136 was effective on phospholipase A2-induced degranulation, although the compound did not directly affect the enzyme activity. In all tests for comparison, KP-136 and DSCG had similar profiles of action and the parallel experiments indicated that KP-136 was a more potent inhibitor of mast cell activation than DSCG, having a DSCG-like membrane stabilizing activity.
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PMID:The protective effect of a new antiallergic agent, KP-136 on mast cell activation: a comparison with disodium cromoglycate. 314 15

A23187-induced histamine release from purified rat mast cells is accompanied by degradation of mast cell phosphatidylcholine. When inhibitors of histamine release such as ethacrynic acid, eicosatetraynoic acid and phenylmethylsulfonylfluoride are added to the mast cell system, the phosphatidylcholine hydrolysis is inhibited along with the release of histamine. A simultaneous striking increase in prostaglandin D2 synthesis by the A23187-treated mast cells suggests that the degradation of phosphatidylcholine is associated with the activation of phospholipase A2. Arachidonic acid, one of the major products formed as a result of this activation, inhibits A23187 and antigen-induced histamine release when added 5 min prior to the histamine release inducers. Lysophosphatidylcholine, the other major product, demonstrates a biphasic effect, stimulating histamine release at low concentrations and inhibiting release at slightly higher concentrations. These findings suggest a histamine release regulating function for arachidonic acid and lysophosphatidylcholine.
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PMID:Possible involvement of phospholipase A2 in A23187-induced histamine release from purified rat mast cells. 615 17

Two vitamins, ascorbic acid (AA) and pyridoxine have been suggested by others as useful drugs for the treatment of bronchial asthma, although the views concerning AA or controversial. We have tested both vitamins in some models of histamine release and experimental anaphylaxis. AA does not inhibit mast cell degranulation induced by phospholipase A and histamine release from isolated rat mast cells induced by compound 48/80 or antigen (egg albumin). On the contrary, in the latter tests pyridoxine exerts inhibition in a range of concentrations from 10(-3)-10(-2) M. We conclude: 1. There is no experimental basis for considering ascorbic acid as a prophylactic antiasthmatic drug as is disodium cromoglycate. 2. Pyridoxine must receive additional basic and clinical investigations in this field.
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PMID:Ascorbic acid and pyridoxine in experimental anaphylaxis. 616 75

The presence of phospholipase A2 in intact rat peritoneal mast cells was investigated by using two synthetic radiolabeled phosphatidylserine (PS) substrates. Incubation of intact cells with 1-oleoyl-2-[3H]oleoyl-PS resulted in the release of a considerable quantity of [3H]oleic acid from the substrate. To establish that [3H]oleic acid release was mediated via direct enzymatic attack at the sn-2 position, we measured release of the [3H]serine moiety from the glycerol backbone of 1,2-dimyristoylphosphatidyl[3H]serine. This activity, which represents the combined actions of phospholipases C and D, was 10-fold lower than [3H]oleic acid release, indicating that neither of these enzymes is required for the release of the preponderance of [3H]oleic acid. These results establish the existence in intact rat mast cells of a phospholipase A2 active toward exogenous PS. Over the concentration range at which exogenous PS activates mast cell secretion, intact mast cells and broken cells possessed nearly equal levels of phospholipase A2 activity, and enzyme activity was 3--4-fold higher toward PS than phosphatidylcholine. Several agents were tested for their ability to inhibit phospholipase A2 in intact mast cells. Of the agents tested, an N-substituted derivative of PS previously identified as an inhibitor of mast cell secretion was shown to be a particularly potent and efficacious inhibitor of mast cell phospholipase A2. The concentration dependence of enzyme inhibition paralleled inhibition of histamine secretion, providing a strong positive correlation between the level of phospholipase A2 in mast cells and the capacity for secretion.
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PMID:Rat mast cell phospholipase A2: activity toward exogenous phosphatidylserine and inhibiton by N-(7-nitro-2,1,3-benzoxadiazol-4-yl)phosphatidylserine. 617 68

Two peptides rich in hydrophobic amino acids have been isolated from venom sacs of the European hornet, Vespa crabro. One peptide (P-2) is structurally and functionally related to the tetradecapeptide mastoparan and has been named mastoparan C. Leu-Asn-Leu-Lys-Ala-Leu-Leu-Ala-Val-Ala-Lys-Lys-Ile-LeuNH2. The other (P-1) is a tridecapeptide with a new sequence: Phe-Leu-Pro-Leu-Ile-Leu-Arg-Lys-Ile-Val-Thr-Ala-LeuNH2 which we have named crabrolin. The peptide releases histamine from rat peritoneal mast cells with a threshold of approximately 2.5 micrograms/ml (congruent to 8 microM). Crabrolin also facilitates the action of purified phospholipase A2 from different sources, but it is not quite as active as mastoparan. It is clearly less active than mastoparan in lysing erythrocytes, and it does not release amylase from dispersed guinea pig pancreatic acini. Given its unique sequence, the principal effect of crabrolin may be neither mast cell degranulation nor phospholipase facilitation, but a yet undiscovered action.
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PMID:Isolation and characterization of two new peptides, mastoparan C and crabrolin, from the venom of the European hornet, Vespa crabro. 620 53

Chrysotile asbestos interacts with mucin-secreting cells of tracheal organ cultures, causing an increase in secretion of mucin into the culture medium. This response occurs in the absence of obvious morphologic damage to tracheal epithelial cells. We speculated that asbestos-induced hypersecretion was regulated by the interaction of fibers with specific carbohydrate residues on the cell surface. To test this hypothesis, lectins, i.e., proteins with a high affinity for mono- and oligosaccharides on the plasma membrane, were added to tissues 30 min before addition of chrysotile. Secretion of mucin into the medium was then determined over a 2-hr period by using incorporation of 3H-glucosamine. Blocking of alpha-D-mannose and alpha-D-glucose residues inhibited chrysotile-induced hypersecretion (p less than 0.05), whereas lectins blocking residues of alpha-D-N-acetylgalactosamine, beta-D-N-acetylglucosamine, alpha-L-fucose and sialic acids were ineffective. Preincubation of cultures with carboxypeptidase A or phospholipase A2, but not with neuraminidase, diminished mucin secretion caused by chrysotile. To determine if the positive surface charge of chrysotile was important in interaction with mucin cells, we examined comparatively the effects of various polycations (cationic ferritin, polylysine, DEAE-dextran) and chrysotile after leaching of fibers to remove Mg2+. Although use of polycations enhanced secretion of mucin, effects were not as striking as those observed with chrysotile. In contrast, leached chrysotile failed to elicit a hypersecretory response. These results suggest the interaction of a positively charged component (presumably Mg2+) of chrysotile with glycolipids and glycoproteins containing terminal residues of alpha-D-mannose or alpha-D-glucose.
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PMID:Studies using lectins to determine mineral interactions with cellular membranes. 631 63

Low molecular weight eosinophil chemotactic factor (ECF), which has previously been demonstrated in mast cells, basophils, neutrophils and eosinophils, was shown to be released by several types of mononuclear phagocytes. Highly purified rat peritoneal macrophages and human monocytes produced ECF on stimulation with the calcium ionophore A23187 (Ion) and with phagocytic stimuli in a time-dependent fashion, whereas lymphocyte- or mast cell-specific stimuli were ineffective. Two murine macrophage lines and a fibroblast cell line (L cells) also generated and secreted ECF with the different stimuli. ECF from macrophages was similar to that from neutrophils in its target cell specificity (eosinophils and neutrophils) and its elution profile on Sephadex G-10 columns (300-500 dalton). ECF secretion from monocytes was not affected by mitomycin C or cycloheximide, whereas indomethacin enhanced and a phospholipase A inhibitor decreased its production. These in vitro findings suggest that, through ECF, mononuclear phagocytes may potentially regulate eosinophil and neutrophil influx to sites of inflammatory reactions.
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PMID:In vitro generation of eosinophil chemotactic factor from human and murine mononuclear phagocytes. 679 47


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